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ABSTRACT Measurement of serum prolactin levels is a common practice in clinical settings, particularly among women of reproductive age. In cases of hyperprolactinemia, identifying macroprolactinemia can help prevent unnecessary investigation and inappropriate treatments. This Position Statement, jointly prepared by the Brazilian Society of Endocrinology and Metabolism (SBEM) and the Brazilian Society of Clinical Pathology/Laboratory Medicine (SBPC/ML), addresses several aspects of macroprolactinemia relevant to clinical practice – including concepts, definitions, epidemiological aspects, measurement techniques, and the role of screening – and discusses some clinical dilemmas.

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ABSTRACT Thermal ablation (TA) encompasses various options such as radiofrequency ablation (RFA), microwave ablation (MWA), laser ablation (LA), and high-intensity focused ultrasound (HIFU). The fundamental principle of these techniques involves generating heat to induce coagulative necrosis of the nodules. The rising incidence of thyroid nodules, most of which are benign, has highlighted the importance of minimally invasive methods that effectively control symptoms, address cosmetic concerns, and achieve volume reduction. The potential complications associated with surgical interventions have driven the widespread adoption of TA modalities, now used not only for symptomatic benign thyroid nodules (BTN), including autonomously functioning thyroid nodules (AFTN), but also for low-risk papillary thyroid microcarcinoma (PTMC). The evidence presented in this consensus has demonstrated the comparable effectiveness of TA to surgery for BTN in terms of volume reduction percentage (VRP), resolution of symptoms, and cosmetic concerns. Similarly, TA could be considered a suitable option for treating AFTN when surgery or radioactive iodine (RAI) is contraindicated, or when patients decline either of these options, offering a comparable effectiveness profile to RAI in terms of normalizing thyroid-stimulating hormone levels. For PTMC, TA may serve as an alternative for patients at high surgical risk or those who decline surgery, showing comparable outcomes to surgery in terms of local recurrence and lymph node metastasis. Additionally, TA exhibits a superior safety profile compared to surgery or RAI, characterized by reduced complications, preservation of thyroid function, and shorter hospitalization durations. While evidence on cost-effectiveness in Latin America remains limited, studies conducted in other countries support the implementation of TA as a first-line treatment option for BTN. The lack of economic assessment specific to AFTN complicates its consideration as a primary treatment choice; however, the effectiveness and safety profile suggest that the widespread adoption of TA as a first-line therapy could be considered for carefully selected patients diagnosed with AFTN or PTMC. The Surgical Affairs Committee of the Latin American Thyroid Society conducted a comprehensive review of TA as a primary treatment modality for benign, autonomously functioning, and malignant thyroid nodules to ensure its appropriate utilization in the field.

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Abstract VitaminD deficiency is a global concern, and calcifediol serves as an alternative to cholecalciferol for achieving and maintaining optimal vitamin D levels, despite the lack of international guidelines for calcifediol supplementation regimens. We present a case involving a 58-year-old patient with osteoporosis and a medical history of type 2 diabetes, obesity, and cirrhosis. Standard treatment with calcium, cholecalciferol, and bisphosphonate was initiated; however, supplementation failed to achieve the target vitamin D levels during follow-up. Subsequently, calcifediol was introduced at a dose of 10 mcg daily, which was increased to 20 mcg daily after one month. Nonetheless, the vitamin D serum concentration rose to 80 ng/mL by the third month, prompting discontinuation of the drug and levels gradually decreased to 28 ng/mL over 2.5 months. Upon the administration of calcifediol at 10 mcg three times a week, serum levels stabilized at 35 ng/mL. Calcifediol offers several advantages over cholecalciferol, including better intestinal absorption, bypassing the need for hepatic hydroxylation, and a more rapid increase in 25-hydroxyvitamin D (25[OH]D) levels. Current guidelines recommend considering calcifediol in cases of obesity, malabsorption syndromes, and chronic hepatic diseases, although optimal dosages remain uncertain. Based on the commercially available tablet in Brazil, we suggest initiating calcifediol at 10 mcg per day and adjusting the dose according to 25(OH)D levels.

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ABSTRACT Immune checkpoint inhibitors have become transformative therapies, significantly enhancing survival outcomes for various neoplasms. However, they often trigger immune-related adverse events, including endocrinopathies. Cushing’s syndrome, characterized by exposure to elevated levels of circulating cortisol, presents a wide range of clinical features and is closely associated with increased morbidity and mortality. This article reports on a case of a patient under checkpoint inhibitor therapy, who developed cyclic adrenocorticotropic hormone-dependent hypercortisolism. The patient exhibited a Cushingoid phenotype, and testing revealed increased cortisol levels following the administration of 1 mg of dexamethasone, indicating endogenous hypercortisolism. Notably, the cortisol levels followed a cyclic pattern, decreasing as the next dose of pembrolizumab neared, thereby linking the hypercortisolism to fluctuations in the medication’s serum concentration. Given the significant morbidity linked to hypercortisolism, it is crucial for physicians prescribing immune checkpoint inhibitors to recognize the potential onset of endocrinopathies with unconventional presentations, such as cyclic hypercortisolism. Such conditions may present diagnostic and therapeutic challenges, ultimately impacting patient survival.

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Abstract Objective: Long non-coding RNAs (lncRNAs) do not encode proteins and are transcripts longer than 200 nucleotides. The precise involvement of lncRNAs in type 1 diabetes mellitus (T1DM) pathogenesis remains unclear. Therefore, this study aimed to analyze the expressions of five lncRNAs in peripheral blood mononuclear cells of individuals with T1DM and without DM. Materials and methods: This study comprised 27 patients with T1DM (cases) and 13 individuals without DM (controls). The case group was divided into two subgroups based on T1DM duration: < 5 years of diagnosis group and long-term diabetes group (≥5 years). LncRNA expression was evaluated by qPCR. Results: MALAT1 and TUG1 were upregulated in patients within the first five years of diagnosis of T1DM compared to the other groups. MEG3 was upregulated in the case group of < 5 years of diagnosis compared to controls. TUG1 and MALAT1 levels were negatively correlated with the duration of T1DM, while TUG1 and MEG3 were positively correlated with glycated hemoglobin levels. Bioinformatics analysis revealed that MALAT1, MEG3, and TUG1 regulate and interact with protein-codifying genes and microRNAs involved in T1DM-related pathways. Conclusion: Our study revealed MALAT1, MEG3, and TUG1 upregulation in patients within the first five years of diagnosis of T1DM.

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ABSTRACT Objective: Metabolic dysfunction-associated steatotic liver disease (MASLD), a worldwide public health challenge with a prevalence of around 25%, is strongly related to obesity and insulin resistance. The present study investigated the possible association between MASLD and the leptin gene (LEP) -2548G>A (rs7799039) polymorphism. Subjects and methods: A total of 250 subjects (125 biopsy-proven MASLD patients and 125 controls) were genotyped for the -2548G>A promoter variant using the PCR-RFLP technique. Results: There was no deviation from Hardy-Weinberg equilibrium for LEP -2548G>A polymorphism in both groups (P > 0.05). A significant association between this gene variant and MASLD was found. The LEP -2548G>A “GG” genotype compared with ‘‘AA+AG’’ genotype was underrepresented in the MASLD patients than controls, even after adjustment for confounding factors (P = 0.016; OR = 0.42, 95% CI = 0.40-0.83). Conclusion: For the first time, our findings demonstrated that the “GG” genotype of LEP -2548G>A gene variant can be a potential protective factor for MASLD. Further studies in other populations, however, are required to support this finding.

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ABSTRACT Objective: Transgender and gender-diverse (TGD) refers to people whose gender identity does not correspond to the sex assigned to them at birth. This study evaluated the knowledge of medical residents at a tertiary hospital in northeastern Brazil regarding healthcare for the TGD population. Materials and methods: This cross-sectional, single-center observational study surveyed medical residents at a tertiary hospital in northeastern Brazil in 2023. It utilized a self-developed online questionnaire, which residents completed voluntarily and anonymously. Descriptive statistics, chi-square analyses, and multivariate logistic regression were applied to the data. Results: A total of 107 residents completed the questionnaire (40.83% of the eligible cohort); most were clinicians (69.15%). All participants identified as cisgender. Nearly all participants considered it important to understand healthcare for TGD patients. About half reported prior education on the topic; gynecology, obstetrics, and endocrinology residents (specialists) demonstrated the highest rates (p = 0.0009). Approximately 40% of the participants were unaware of where to refer TGD people for specialized care in hormone therapy and gender-affirming surgeries (p = 0.007). Lack of experience (p = 0.002) was the primary reason among the 30 residents who felt insecure about providing healthcare to TGD patients. Conclusion: Residents acknowledge the importance of this field in their practice but demonstrate a lack of specific knowledge and prior education.

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ABSTRACT Objective: Obesity prevalence is increasing in Brazil. Real-world observational data were used to understand clinical weight management practice, and the economic and health-related quality-of-life (HRQoL) impact of obesity. Materials and methods: Data were derived from the Adelphi Real World Obesity Disease Specific Programme (DSP)™, a cross-sectional survey of people with obesity (PwO) and treating physicians, conducted in Brazil May-October 2022. Physicians reported demographic/clinical characteristics and current/previous weight management. PwO reported emotional/financial impact of obesity, and completed patient-reported outcomes on HRQoL, and activity/work impairment. Results: In total, 99 physicians reported on 895 PwO. Mean ± SD PwO age was 43.1 ± 13.7, majority were female (60.9%) and white (71.7%). Mean ± SD BMI at survey was 33.8 ± 9.4 with 40.5%, 23.2% and 11.1% of PwO having class 1, 2 or 3 obesity. Weight management was most commonly at PwO request (43.4%), and consisted of prescription weight loss drug (53.6%), and dietician or physician-supervised diets (79.9% and 55.1%). Most PwO reported financial impact due to obesity treatment and reported being bothered/embarrassed by their weight. SF-36v2 physical summary scores ranged from 52.4 ± 9.3 to 45.6 ± 8.6 and mental summary scores from 45.5 ± 9.3 to 42.2 ± 12.3 (BMI < 30 to class 3 obesity). Overall work and activity impairment ranged from 20.0 ± 22.7 to 42.4 ± 28.4 (BMI < 30 and class 2 obesity) and from 24.7 ± 25.2 to 43.2 ± 32.5 (BMI < 30 to class 3 obesity), and 3.2% did not work due to obesity. Conclusion: PwO have a substantial impact on work, and financial, emotional and quality-of-life burden. Our data highlight the need for more efficacious obesity management, to help reduce work and activity impairment, improve quality of life.

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ABSTRACT Objective: To evaluate cyclical and seasonal variation in the incidence of type 1 diabetes mellitus (T1DM) from 1985 to 2016 in Bauru, São Paulo, Brazil. Subjects and methods: This was a retrospective longitudinal study. Clinical data were collected for individuals known to have T1DM, who aged from 0-14 years, residing in Bauru, São Paulo State, and followed at a local endocrinology clinic from 1985 to 2016. Incidence rates were calculated annually and grouped into quadrennial intervals. Trends were analyzed using Joinpoint Regression to estimate annual percentage changes. Poisson regression models assessed cyclical and seasonal patterns over various periods (3- to 7.5-year cycles). Seasonal variation was evaluated using the Akaike Information Criterion and chi-square likelihood ratios to assess model fit. Results: Among the 298 included patients, the mean annual incidence was 12.1 per 100,000 person-years (95% CI: 10.7-13.4), with an average annual increase of 2.77% (95% CI: 1.3-4.3%). A significant cyclical variation of 18% every 7.5 years was observed, with girls exhibiting a 22.9% variation every 5 years. No cyclical pattern was identified for boys. Seasonal analysis revealed higher amplitudes among girls (±26.4%) and in the 5-9.99-year age group (±26.2%), predominantly during colder months. Conclusion: T1DM cyclical variations with a 7.5-year cycle were observed, with girls showing a pronounced variation and a distinct 5-year cycle. Seasonal variations were found among girls, particularly in the 5-9.99-year age group. Outbreaks of H1N1 and dengue, along with the lowest temperatures, coincided with higher incidence rates, aligning with the 7.5-year cycles. Targeted health policies are needed to mitigate the impact of these factors, supporting surveillance, early diagnosis, and preventive strategies for T1DM.

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ABSTRACT Objective: To identify maternal and neonatal outcomes in pregnancies with early versus late gestational diabetes mellitus (GDM) diagnosis, considering healthcare access in a low- to middle-income area of Brazil. Subjects and methods: This retrospective study included women diagnosed with either early GDM (diagnosed before 20 weeks, based on fasting plasma glucose) or late GDM (diagnosed by 24-28 weeks, via oral glucose tolerance test), according to the IADPSG criteria, who received prenatal care at a hospital in southern Brazil. Maternal outcomes included gestational hypertension, pre-eclampsia, cesarean section or instrumented vaginal delivery, and need for intensive care after birth. Perinatal outcomes were assessed based on the adequacy of birth timing and weight for gestational age, the need for neonatal intensive care, shoulder dystocia or fractures, neonatal hypoglycemia and mortality. Logistic regression was used to adjust for possible confounders, with results presented as odds ratios (OR) and 95% confidence intervals (CI). Results: A total of 320 women with GDM (mean age 32.9 ± 6.5 years) were included: 164 (51.2%) with early GDM and 156 (48.8%) with late GDM. The primary composite maternal outcome was more frequent in late GDM (43.6% versus 29.3%; OR 1.87; 95% CI 1.15-3.03), as well as perineal laceration (OR 2.45; 95% CI 1.22-4.84). No significant differences were found between groups in the primary composite neonatal outcome, prematurity, or macrosomia rates. Conclusion: In this low-income population in southern Brazil, early GDM diagnosis led to more prenatal consultations and pharmacological treatment, which may have contributed to reduced adverse maternal outcomes.

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ABSTRACT Objective: Dyslipidemia is a common cardiovascular risk factor, with ongoing debate over whether lipid profile assessment, with or without fasting, affects the accuracy of cardiovascular risk evaluation. The objective of this study is to evaluate the effect of fasting status on lipid profile values and the prevalence of dyslipidemia. Subjects and methods: A total of 269 adults (20-69 years) from Vitória-ES (Brazil) were included. Two blood samples were collected on the same day: one in the morning after a 10-12-hour fast and the other in the afternoon, post-lunch (1-5 pm). Dyslipidemias were classified according to the Brazilian Guidelines. Results: The percentage of participants classified with low HDL-c (male: 54.2 vs. 38.2%, p < 0.001; female: 29.7 vs. 15.2%, p < 0.001) and hypertriglyceridemia (male: 59.5 vs. 26.7%, p < 0.001; female: 50.0 vs. 22.5%, p < 0.001) was higher in the non-fasting state. Furthermore, HDL-c levels were higher in after fasting. Triglyceride levels were higher in the non-fasting state, while LDL-c concentrations were slightly reduced in the non-fasting state. Without fasting, 85 individuals previously classified as having normal TG were reclassified as having hypertriglyceridemia, and 41 individuals previously classified as having normal HDL-c were reclassified as having low HDL-c. Conclusion: The feeding state is key to detecting and managing dyslipidemias, especially hypertriglyceridemia and low HDL-c. Removing the fasting requirement could improve cardiovascular risk identification, increase patient adherence to testing and treatment. However, the significant differences in the lipid profile concentrations must be considered in the patient’s management in the clinical practice.

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Abstract Objective: This study assessed the effects of bariatric surgery on the anthropometric profile and cardiometabolic outcomes of women aged 28-66. Additionally, it compared data from patients under and over 50 years old who underwent bariatric surgery at a reference hospital between 2010 and 2018. Materials and methods: A retrospective cohort study analyzed the medical records of female patients aged 28-66 years at a weight control program who underwent bariatric surgery at a reference hospital over a period of 8 years. Patient profiles were characterized, normality was tested (Shapiro-Wilk), and comparisons were made between preoperative and follow-up periods (Friedman’s ANOVA test). Age groups were also compared (Mann-Whitney test). The significance level was set at 5% (p < 0.05). Results: Patients under 50 years of age had significantly greater weight loss than those over 50 years (p=0.017). However, there was no significant difference in the loss of excess weight, BMI, blood pressure, or laboratory parameters between the two groups. Conclusion: Our results reinforced the consensus that bariatric surgery is an effective treatment for overweight individuals, improving weight loss and metabolic health. Although the hormonal changes of menopause contribute to the development of an unfavorable cardiometabolic profile, bariatric surgery was equally effective in menopausal women as in younger patients in the population studied.

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Abstract Objective: Extranodal extension (ENE) is acknowledged as a significant prognostic factor associated with recurrence, distant metastasis, and reduced disease-specific survival in patients with papillary thyroid carcinoma. However, the impact of the extent of extranodal extension on the clinical outcomes of these patients remains insufficiently understood. This study aimed to estimate the risk of detecting distant metastasis in patients with varying degrees of ENE according to a novel stratification method. Materials and methods: This retrospective study utilizes medical records and slide reviews of papillary thyroid cancer patients who underwent therapeutic neck dissection. A new stratification system was developed, based on the circumferential rupture of the lymph node capsule. It is defined as Focal ENE when less than one-third of the lymph node capsule is ruptured and as Diffuse ENE when one-third or more of the capsule is involved. Results: Eighty-nine patients participated in the study, with 19% diagnosed with distant metastasis within a 96-month follow-up period. The presence of diffuse extranodal extension was associated with a risk approximately six times higher than in patients without ENE for the detection of distant metastasis at 96 months, after adjustment for age group (HR = 6.41; 95% CI: 1.7-23.8; p = 0.006). Conclusion: A greater extent of extranodal extension is linked to a heightened risk of detecting distant metastasis and should thus be considered in the therapeutic decision-making process.

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Abstract Objective: The aim of this study is to demonstrate the real-life efficacy of BRAF and MEK inhibitors in patients with advanced thyroid cancer. Subjects and methods: This retrospective study evaluated the clinical efficacy of either a BRAF inhibitor (dabrafenib) alone or a BRAF inhibitor (dabrafenib) in combination with a MEK inhibitor (trametinib) in the treatment of 10 patients diagnosed with metastatic BRAF-mutant RAI refractory thyroid cancer. The primary endpoint was the investigator-assessed overall response rate (ORR). Results: The median patient age was 68 years, 60% were men, and all patients were diagnosed with progressive BRAF V600E-mutant RAI-refractory papillary thyroid carcinoma (PTC). In total, 70% of the patients had been previously treated with multikinase inhibitors. One (1%) patient received a BRAF inhibitor alone and 9 (90%) patients received a combination of BRAF and MEK inhibitors. After treatment, 2 (20%) patients achieved a complete response, 5 (50%) patients achieved a partial response, 1 (10%) patient experienced stable disease, and 1 (10%) patient experienced progressive disease. Seven (70%) patients had an objective response rate (ORR) (complete or partial response). Progression-free survival (PFS) was 70%, 40%, 30%, and 30% at 6, 12, 18, and 24 months, respectively. The 12-month overall survival (OS) rate was 90%. Conclusion: Dabrafenib in combination with trametinib was well tolerated and resulted in substantial clinical benefit, with notable PFS and sustained OS, even as a second-line treatment, in patients diagnosed with metastatic, progressive BRAF V600E-mutated, RAI-refractory thyroid cancer.

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Abstract Objective: Graves’ disease (GD), an autoimmune disorder causing hyperthyroidism, is often diagnosed using 99mTc scintigraphy. While increased thyroidal 99mTc uptake with homogenous distribution is typical, atypical patterns (normal or heterogeneous) occur. This study aimed to investigate the determinants of these atypical uptake patterns in GD. Subjects and methods: Re-trospective records review identified 238 GD patients diagnosed between January 2022 and December 2024. Normal 99mTc uptake (0.4%-3%) and heterogeneous distribution patterns were defined based on scintigraphy. Relevant clinical and biochemical data were compared between typical and atypical pattern groups. Results: Normal 99mTc uptake was observed in 25/238 (10.5%). Compared to increased uptake, it was associated with lower FT4, T3 levels (p < 0.01) and TRAb levels (p = 0.01) with similar prevalence of heterogeneous distribution (p > 0.05). Compared to homogeneous uptake, heterogeneous uptake subgroup (n = 30/238, 12.6%) had similar TRAb/T3 levels (p > 0.05) with lower FT4 (p = 0.04); and were more likely to have goiter grade > 1 (p < 0.05). Age, gender, smoking and thyroid eye disease were not associated with either atypical uptake pattern. In regression analysis, lower TRAb was associated with normal uptake (OR 0.798, 95% CI 0.660-0.965, p = 0.02), and goitre grade > 1 was associated with heterogeneous uptake (OR 4.34, 95% CI 1.25-15.03, p = 0.01). Conclusion: Atypical 99mTc uptake patterns were observed in a notable subset of GD. Normal uptake subgroup may reflect a mild evolving disease stage with lower TRAb, while heterogeneous uptake was primarily linked to increased thyroid size. These findings highlight the importance of integrating clinical and biochemical data when interpreting thyroid scintigraphy in suspected GD.

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ABSTRACT Objective: The relationship between liver health and glycaemic control in elderly patients with diabetes remains poorly understood. In this study, the value of liver elastography in identifying associations with poor glycaemic control among elderly patients with type 2 diabetes mellitus was investigated. Subjects and methods: In total, 90 elderly patients (aged ≥ 60 years) with type 2 diabetes mellitus were enrolled in this prospective observational study. All participants underwent liver elastography using FibroScan® and continuous glucose monitoring (CGM). Liver stiffness measurements (LSMs) and the controlled attenuation parameter (CAP) were obtained. Glycaemic control was assessed through multiple parameters, including the time in range (TIR), time above range (TAR), glycaemic variability, and mean glucose levels. Poor glycaemic control was defined as a TIR < 70%. The mean age of the participants was 64.0 ± 10.5 years, with 65.6% being female. The mean liver stiffness was 6.1 ± 7.8 kPa, and the mean CAP was 266.0 ± 54.7 dB/m. Results: Patients with higher liver stiffness (>8.0 kPa) had a significantly lower TIR (68.7% versus 83.5%, p<0.001) than those with normal liver stiffness (<5.5 kPa). LSMs were strongly negatively correlated with the TIR (r = -0.42, p < 0.001) and positively correlated with the mean glucose level (r = 0.38, p < 0.001). Multivariate analysis revealed that increased liver stiffness was independently associated with poor glycaemic control (adjusted OR = 1.28, 95% CI: 1.14-1.44; p < 0.001). Conclusion: ROC analysis revealed an exploratory LSM cut-off value of 6.8 kPa for association with poor glycaemic control (AUC = 0.76; sensitivity = 71.2%; specificity = 78.9%). LSMs via transient elastography are independently associated with poor glycaemic control in elderly patients with type 2 diabetes. An LSM threshold of 6.8 kPa may help identify patients who are more likely to present with poor glycaemic control.

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ABSTRACT Objective: It is well established that serum levels of TSH receptor antibodies (TRAb) rise after radioiodine (131I) therapy for Graves’ disease (GD). However, it remains unclear whether these post-therapy autoantibodies are predominantly TSH receptorstimulating immunoglobulins (TSI) and how their persistence might affect treatment outcomes. Subjects and methods: In this prospective study, 39 patients with GD underwent 131I therapy. Serum TRAb (measured by competitive electrochemiluminescence, ECLIA) and TSI (measured by an IMMULITE® 2000/2000 XPi TSI assay) were evaluated at baseline and at 1, 2, 3, 6, 9, and 12 months post-therapy. More than 7% increase from baseline was considered a significant rise. Results: At diagnosis, all 39 patients tested positive for TRAb, while 38 tested positive for TSI. Both TRAb and TSI levels rose significantly between months 2 and 4 post-131I, followed by a progressive decline by months 9 to 12. TSI increased in 72% of patients; of these, 93% showed a gradual decrease but remained higher than baseline in 58% at 12 months. Patients with thyroid eye disease (TED), longer disease duration, or higher baseline TSI more frequently exhibited persistent elevation at one year. Despite the persistence of TSI, all patients achieved control of thyrotoxicosis (euthyroid or hypothyroid states). Conclusion: Radioiodine therapy leads to an increase in TSI, which can remain elevated for up to 12 months in more than half of GD patients. These findings suggest potential benefits of measuring TSI for guiding management decisions, particularly regarding antithyroid drug discontinuation and pregnancy planning.

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ABSTRACT Objective: To evaluate and to compare machine learning models for predicting hypertension in patients with diabetes using routine clinical variables. Methods: Using Behavioral Risk Factor Surveillance System data, models were trained on 35,346 individuals with seven variables (“HighChol”, “BMI”, “Smoker”, “PhysActivity”, “Sex”, and “Age”) to predict the occurrence of hypertension in patients with diabetes (“HTNinDM”). Models included neural network, gradient boosting, random forest, Adaptive Boosting, and logistic regression. Performance was assessed by area under the curve, accuracy, precision, and recall, and F1 score using cross-validation. Class imbalance was addressed via diverse models. Feature importance was evaluated by permutation importance of a random forest model. Results: The neural network model achieved the best performance with area under the curve 0.689, accuracy 76.5%, precision 76.3%, recall 98.8%. Gradient boosting models performed similarly. Age and body mass index were the top predictors. Conclusion: Machine learning models show potential for identifying patients with diabetes at high hypertension risk using routine clinical data. A neural network model achieved excellent predictive performance.

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ABSTRACT Objective: Genetic abnormalities in ion channels that regulate the depolarization of adrenal glomerular cell plasma membranes have been identified as a cause of primary aldosteronism (PA) due to aldosterone-producing adenoma (APA). This study aimed to evaluate somatic variants in the KCNJ5, CACNA1D, CLCN2, ATP1A1, ATP2B3, GNAQ, GNA11, and CTNNB1 genes, assess the genotype-phenotype correlation, and analyze the outcomes in patients with APA from a heterogenic ethnic population. Subjects and methods: Clinical, biochemical, and molecular data were obtained from 32 patients. Results: Pathogenic variants (PVs) were identified in 43.7% (14/32) of the patients. PVs occurred in 31.2% (10/32) of the KCNJ5 gene: p.Leu168Arg (15.6%), p.Gly151Arg (9.3%), p.Glu145Gln (3.2%), and p.Gly151_Tyr152del (3.2%). In the CLCN2 gene, two PVs (6.25%), p.Pro48Arg and p.Ala195Thr, were identified; the latter was found in association with p.Glu145Gln in the KCNJ5 gene within the same APA. Additionally, two PVs were found in ATPase genes: p.Leu104Arg in ATP1A1 (3.2%) and p.Leu425_Val426del in ATP2B3 (3.2%). No PVs were identified in the other examined genes. Patients with KCNJ5 PVs were predominantly female (90% vs. 45.5%; p = 0.01), had an earlier age of PA diagnosis (38 vs. 54 years; p = 0.04), and exhibited fewer electrocardiogram abnormalities (20% vs. 59%; p = 0.04). Patients with PVs across all studied genes also showed an earlier age at PA diagnosis (p = 0.02). The Primary Aldosteronism Surgical Outcome score revealed that 37.5% of patients met clinical/biochemical cure criteria, 12.5% showed partial improvement in both, while 50% achieved complete biochemical but not clinical remission. Patients carrying PVs had a higher rate of complete clinical and biochemical cure (66.7% vs. 33.3%; p = 0.05). Conclusion: Identifying PVs in this study enhances our understanding of the genetic landscape in Brazilian patients with primary aldosteronism.

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ABSTRACT Kallmann syndrome (KS) is a rare genetic disorder characterized by hypogonadotropic hypogonadism and anosmia or hyposmia, stemming from the defective migration of GnRH and olfactory neurons during embryogenesis. This study investigated a multigenerational family with KS, identifying novel mutations in the ANOS1 (c.78_108del, X-linked) and GNRHR (c.974del, autosomal recessive) genes through genetic testing. Affected males carrying the ANOS1 mutations displayed a range of phenotypes, all of which were associated with hypogonadism and varying degrees of anosmia. Furthermore, isolated mutations in the GNRHR gene were linked to milder forms of hypogonadism. Individuals possessing mutations in both genes exhibited more severe phenotypes, suggesting a digenic mode of inheritance. These findings broaden the known mutational landscape of KS, illustrating how variations and combinations of mutations in multiple genes can lead to diverse symptoms and levels of severity within the same disorder. By integrating clinical and genetic data, this research enhances understanding of the intricate mechanisms underlying KS, highlighting the value of next-generation sequencing in revealing oligogenic contributions to endocrine disorders for improved diagnostics, management, and genetic counseling.